ROLE OF MONOKINES IN B CELL ABNORMALITIES IN AIDS

单核因子在艾滋病 B 细胞异常中的作用

• 批准号: 3142551
• 负责人: CHRISTY SANDBORG
• 金额: $ 12.82万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-03-01 至 1993-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3142551
• 关键词: AIDS; B lymphocyte; Epstein Barr virus; HIV infections; antibody neutralization test; bioassay; enzyme linked immunosorbent assay; gel electrophoresis; human subject; immunoglobulins; interleukin 1; interleukin 6; laboratory mouse; leukocyte activation /transformation; lymphoma; macrophage; monokines; northern blottings; tissue /cell culture

B cell hyperactivity is a common immune abnormality in ARC and AIDS and may represent a major predisposing factor leading to the development of B cell lymphomas. The cause for this B cell hyperactivity is not completely understood at this time, but impaired T cell function, B cell dysregulation and massive EBV infection are likely to be important contributing factors. The monokines, IL-1 alpha, IL-1 beta, IL-6 and a novel 6-9 K MW factor, are increased in mononuclear cell (PBM) cultures from patients with AIDS and in vitro HIV infection of normal macrophages. Among their other activities, these monokines stimulate B cell growth and/or Ig production. The long term objective of this proposal is to evaluate the role of these monokines in B cell hyperactivity in AIDS. The specific aims are: I. To characterize the interaction of IL-l alpha, IL-l beta, IL- 6,and the 6-9 K MW factor on HIV-infected and uninfected EBV- transformed B cells. Production and release of these factors by infected and uninfected EBV cell lines will be determined by chromatographic separation, testing for the factors by bioassay, neutralization of bioactivity with specific antibodies, immunoassay, and Northern blot analysis. The effect of these monokines on growth and Ig production of HIV infected and uninfected EBV cell lines will be determined. The effect of these factors on the susceptibility of normal B cells to EBV transformation will be determined by limiting dilution analysis. II. To characterize the mode of action of 6-9 K MW factor on normal B cells. The effect of this factor on resting, Staphylococcus aureus Cowan strain I (SAC) induced B cell proliferation and Ig production, and dependence on or synergy with IL-l alpha, IL-l beta, IL-6 and other known B cell factors will be determined. The contribution of T cells and M0 will be assessed. The effect of these factors on B cell subpopulations will be determined.

B细胞过度活跃是ARC和AIDS中常见的免疫异常 可能是导致 B细胞淋巴瘤的发展。 导致这种B细胞的原因 多动症在这个时候还没有完全被理解，但是 T细胞功能受损、B细胞失调和大量EBV 感染很可能是重要因素。 的 单核因子、IL-1 α、IL-1 β、IL-6和新的6-9 KMW因子， 在来自患者的单核细胞（PBM）培养物中， 艾滋病与体外HIV感染的正常巨噬细胞。 他们的 其他活性，这些单核因子刺激B细胞生长和/或 IG生产。 这项建议的长远目标是 评估这些单核因子在B细胞过度活跃中的作用， 艾滋病 具体目标是： I. 为了表征IL-1 α、IL-1 β、IL-1 β和IL-10之间的相互作用， 6和6-9 K MW因子对HIV感染和未感染EBV-1的影响。 转化的B细胞。 这些因素的产生和释放， 感染和未感染的EBV细胞系将通过 色谱分离，生物测定法检测因子， 用特异性抗体中和生物活性， 免疫测定和北方印迹分析。 这些的作用 单核因子对HIV感染者生长和IG产生的影响， 将确定未感染的EBV细胞系。 这些影响 影响正常B细胞对EB病毒易感性的因素 转化将通过有限稀释分析来确定。 二. 为了表征6-9 K MW因子对 正常的B细胞。 这个因素对休息的影响， 金黄色葡萄球菌科万菌株I（SAC）诱导的B细胞 增殖和IG产生，以及依赖于或协同作用 IL-1 α、IL-1 β、IL-6和其它已知的B细胞因子将被 测定 将评估T细胞和M0的贡献。 这些因素对B细胞亚群的影响将在 测定